Innate immune system activation in zebrafish and cellular models of Diamond Blackfan Anemia.

Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The Innate immune system can be activated by endogenous nucleic acids from non-processed pre-rRNAs, DNA damage, and apoptosis that occurs in DBA. Recognition by toll like receptors (TLRs) and Mda5-like sensors induces interferons (IFNs) and inflammation. Dying cells can also activate complement system. Therefore we analyzed the status of these pathways in RP-deficient zebrafish and found upregulation of interferon, inflammatory cytokines and mediators, and complement. We also found upregulation of receptors signaling to IFNs including Mda5, Tlr3, and Tlr9. TGFb family member activin was also upregulated in RP-deficient zebrafish and in RPS19-deficient human cells, which include a lymphoid cell line from a DBA patient, and fetal liver cells and K562 cells transduced with RPS19 shRNA. Treatment of RP-deficient zebrafish with a TLR3 inhibitor decreased IFNs activation, acute phase response, and apoptosis and improved their hematopoiesis and morphology. Inhibitors of complement and activin also had beneficial effects. Our studies suggest that innate immune system contributes to the phenotype of RPS19-deficient zebrafish and human cells

Building a Business Analytics Platform For Enhancing Commercial Beekeepers’ Performance

This project defines and builds a comprehensive data platform that records data for bee management actions and natural world inputs and the performance results flowing from those actions and conditions. The collection and management of this data will allow for the application of advanced data analytics techniques that will lead to a better understanding and evaluation of the economic and best management practices for commercial beekeepers and growers of pollinated crops. Together these will lead to a better design and utilization of smart hive technologies for hive management and the development of an intelligent hive management system

Immunological Responses Elicited by Different Infection Regimes with Strongyloides ratti

Nematode infections are a ubiquitous feature of vertebrate life. In nature, such nematode infections are acquired by continued exposure to infective stages over a prolonged period of time. By contrast, experimental laboratory infections are typically induced by the administration of a single (and often large) dose of infective stages. Previous work has shown that the size of an infection dose can have significant effects on anti-nematode immune responses. Here we investigated the effect of different infection regimes of Strongyloides ratti, comparing single and repeated dose infections, on the host immune response that was elicited. We considered and compared infections of the same size, but administered in different ways. We considered infection size in two ways: the maximum dose of worms administered and the cumulative worm exposure time. We found that both infection regimes resulted in Th2-type immune response, characterised by IL4 and IL13 produced by S. ratti stimulated mesenteric lymph node cells, anti-S. ratti IgG1 and intestinal rat mast cell protease II (RMCPII) production. We observed some small quantitative immunological differences between different infection regimes, in which the concentration of IL4, IL13, anti-S. ratti IgG1 and IgG2a and RMCPII were affected. However, these differences were quantitatively relatively modest compared with the temporal dynamics of the anti-S. ratti immune response as a whole

The Regulation of Pulmonary Immunity

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.No evidence has emerged which suggests that the principles of immunity derived from studies on cells from other body sites are contradicted in the lung and its associated lymphoid tissue. What is clear, however, is that the environment dictates the types of cells, their relationship to one another, and what perturbing events will set in motion either the development of an "active" immune response or tolerance. Investigating mechanisms for the development of lung immunity has increased our understanding of how human diseases develop and is continuing to suggest new ways to manipulate pulmonary immune responses. Demonstration that lung cells regulate both nonspecific inflammation and immunity through the expression of adhesion molecules and the secretion of cytokines offers hope for ways to design more effective vaccines, enhance microbial clearance in immunosuppressed hosts, and to suppress manifestations of immunologically mediated lung disease. Important lung diseases targeted for intensive research efforts in the immediate future are tuberculosis, asthma, and fibrotic lung disease. Perhaps even the common cold might be conquered. Considering the pace of current research on lung immunity, it may not be too ambitious to predict that these diseases may be conquered in the next decade

Design tools for interdisciplinary translation of material experiences

Designers increasingly have the opportunity to influence the development of materials as they emerge from the laboratory. In order for this to be successful, designers need to be able to communicate effectively with materials scientists so that materials can be developed with desired functionalities and properties. This paper reviews evidence in favour of using isomorphic sets of material stimuli as tools to bridge the disciplinary gap between designers and materials scientists. We show how these isomorphic sets and their accompanying experiments can be used to translate between the two communities, and to systematically explore the relationship between the technical attributes of materials and subjective experiences of their sound, taste and feel. This paper also explores the limitations of psychophysical approaches and other quantitative techniques for elucidating material experience, and suggests new possibilities for interdisciplinary collaborations that draw on ethnographic approaches

Radio Jet Feedback and Star Formation in Heavily Obscured Quasars at Redshifts ~0.3-3, I: ALMA Observations

We present ALMA 870 micron (345 GHz) data for 49 high redshift (0.47<z<2.85), luminous (11.7 < log L(bol) (Lsun) < 14.2) radio-powerful AGN, obtained to constrain cool dust emission from starbursts concurrent with highly obscured radiative-mode black hole (BH) accretion in massive galaxies which possess a small radio jet. The sample was selected from WISE with extremely steep (red) mid-infrared (MIR) colors and with compact radio emission from NVSS/FIRST. Twenty-six sources are detected at 870 microns, and we find that the sample has large mid- to far-infrared luminosity ratios consistent with a dominant and highly obscured quasar. The rest-frame 3 GHz radio powers are 24.7 < log P3.0 GHz (W/Hz) < 27.3, and all sources are radio-intermediate or radio-loud. BH mass estimates are 7.7 < log M(BH) (Msun) < 10.2. The rest frame 1-5 um SEDs are very similar to the "Hot DOGs" (Hot Dust Obscured Galaxies), and steeper (redder) than almost any other known extragalactic sources. ISM masses estimated for the ALMA detected sources are 9.9 < log M(ISM) (Msun) < 11.75 assuming a dust temperature of 30K. The cool dust emission is consistent with star formation rates (SFRs) reaching several thousand Msun/yr, depending on the assumed dust temperature, however we cannot rule out the alternative that the AGN powers all the emission in some cases. Our best constrained source has radiative transfer solutions with ~ equal contributions from an obscured AGN and a young (10-15 Myr) compact starburst.Comment: 29 pages, 8 figures. To appear in Astrophysical Journal. Update on Sept 14 to correct the ALMA proposal id. to ADS/JAO.ALMA#2011.0.00397.S and to add a missing acknowledgemen

A microarray analysis of gene expression in the free-living stages of the parasitic nematode Strongyloides ratti

BACKGROUND: The nematode Strongyloides ratti has two adult phases in its lifecycle: one obligate, female and parasitic and one facultative, dioecious and free-living. The molecular control of the development of this free-living generation remains to be elucidated. RESULTS: We have constructed an S. ratti cDNA microarray and used it to interrogate changes in gene expression during the free-living phase of the S. ratti life-cycle. We have found very extensive differences in gene expression between first-stage larvae (L1) passed in faeces and infective L3s preparing to infect hosts. In L1 stages there was comparatively greater expression of genes involved in growth. We have also compared gene expression in L2 stages destined to develop directly into infective L3s with those destined to develop indirectly into free-living adults. This revealed relatively small differences in gene expression. We find little evidence for the conservation of transcription profiles between S. ratti and S. stercoralis or C. elegans. CONCLUSION: This is the first multi-gene study of gene expression in S. ratti. This has shown that robust data can be generated, with consistent measures of expression within computationally determined clusters and contigs. We find inconsistencies between EST representation data and microarray hybridization data in the identification of genes with stage-specific expression and highly expressed genes. Many of the genes whose expression is significantly different between L1 and iL3s stages are unknown beyond alignments to predicted genes. This highlights the forthcoming challenge in actually determining the role of these genes in the life of S. ratti

A NuRD Complex from Xenopus laevis Eggs Is Essential for DNA Replication during Early Embryogenesis.

DNA replication in the embryo of Xenopus laevis changes dramatically at the mid-blastula transition (MBT), with Y RNA-independent random initiation switching to Y RNA-dependent initiation at specific origins. Here, we identify xNuRD, an MTA2-containing assemblage of the nucleosome remodeling and histone deacetylation complex NuRD, as an essential factor in pre-MBT Xenopus embryos that overcomes a functional requirement for Y RNAs during DNA replication. Human NuRD complexes have a different subunit composition than xNuRD and do not support Y RNA-independent initiation of DNA replication. Blocking or immunodepletion of xNuRD inhibits DNA replication initiation in isolated nuclei in vitro and causes inhibition of DNA synthesis, developmental delay, and embryonic lethality in early embryos. xNuRD activity declines after the MBT, coinciding with dissociation of the complex and emergence of Y RNA-dependent initiation. Our data thus reveal an essential role for a NuRD complex as a DNA replication factor during early Xenopus development